The discovery of novel ruthenium metallopharmaceuticals is highly dependent on its
coordination chemistry. As emphasized in Chapter 1, the biodistribution pathway of
a potential ruthenium metallopharmaceutical depends on its oxidation state, aqueous
solubility and the size of its metallic core. Recent developments are geared towards
the utilization of biocompatible ligands which may facilitate biodistribution and finetune
solubility in the blood stream of the formulated ruthenium anticancer agents.
This design approach has motivated us to explore the coordination behaviour of
multidentate N-donor ligands incorporating various biologically active components
(viz. uracil, antipyrine, chromone or benz(imidazole/othiazole) moieties) towards the
diamagnetic ruthenium(II) core. The resultant ruthenium compounds were
characterized via various spectroscopic techniques and structural elucidations were
confirmed using single X-ray analysis. The structural elucidations were
complemented with electro-analytical and DFT studies.
In Chapter 3, the coordination reactions of trans-[Ruᴵ̍ᴵCl₂(PPh₃)₃] with Schiff bases
derived from 5,6-diamino-1,3-dimethyl uracil (H₂ddd) are reported. In the
diamagnetic ruthenium(II) complexes, trans-[RuCl(PPh₃)₂(Htdp)](1) {H₂tdp = 5-
((thiophen-3-yl)methyleneamino)-6-amino-1,3-dimethyluracil} and trans-
[RuCl(PPh₃)₂(Hsdp)](2) {H₂sdp = 5-(2-(methylthio)benzylideneamino)-6-amino-1,3-
dimethyluracil}, the Schiff base ligands (i.e. Htdp and Hsdp) act as monoanionic
tridentate chelators. Similarly, the diimine H₃ucp chelator coordinated as a
monoanionic tridentate moiety in complex 3, [Ru̍ᴵ̍ᴵCl(PPh₃)(H₃ucp)] (H₄ucp = 2,6-bis-
((6-amino-1,3-dimethyluracilimino)methylene)pyridine). Upon reacting 5-(2-
hydroxybenzylideneamino)-6-amino-1,3-dimethyluracil (H₃hdp) with the metal
precursor, the paramagnetic complex, trans-[Ru̍ᴵᵛCl₂(ddd)(PPh₃)₂](4) was isolated, in
which the bidentate dianionic ddd co-ligand was formed by hydrolysis. The presence
of the paramagnetic metal centre for 4 was confirmed by ESR spectroscopy. DFT
studies of complex 3 were conducted to provide insight into its intrinsic solid state
structural features. The redox properties were probed via cyclic voltammetry:
complexes 1, 2 and 4 exhibited comparable electrochemical behaviour with half-wave
potentials (E½) at 0.70 V (for 1), 0.725 V (for 2) and 0.68 V (for 4) vs Ag|AgCl
respectively while the attained half-wave potential (0.37 V vs Ag|AgCl) of 3 was
significantly lower.
Chapter 4 focuses on the isolation of novel ruthenium(II/III) compounds from the
respective reactions of the metal precursor, trans-[RuCl₂(PPh₃)₃] with multidentate
Schiff base ligands bearing the chromone and antipyrine moieties. From these
coordination reactions of trans-[RuCl₂(PPh₃)₃] with 4-((pyridine-2-
ylimino)methylene)-chromone (pch) and 2,6-bis-((antipyrineimino)
methylene)pyridine (bpap); the ruthenium(II/III) complexes: trans-P, cis-Cl-
[Ru̍ᴵ̍ᴵ̍ᴵ(pch)Cl₂(PPh₃)₂] (1) and cis-[RuCl₂(bpap)(PPh₃)] (2) were formed, respectively.
The presence of the paramagnetic metal centre of 1 was confirmed via room
temperature solution ESR spectroscopy. The more delocalized nature of the diimine
chelator of 2 promotes faster electron transfer resulting in a lower redox potential in
contrast to the mono-imine chelator of 1. The electronic spectra of the metallic
compounds exhibited common intraligand Л-Л* and red-shifted Metal-to-Ligand-
Charge-Transfer electronic transitions whilst a d-d electronic transition was only
observed for the paramagnetic compound 1.
In Chapter 5, the analogous chelating behaviour of bidentate N,O-donor heterocyclic
ligands which coordinated in a ‘2+2’ coordination mode, is described. The 1:2 molar
ratio reactions of trans-[RuCl₂(PPh₃)₃] with 2-hydroxyphenylbenzimidazole (Hobz)
and 2-hydroxyphenylbenzothiazole (Hobs), respectively led to the formation of the
diamagnetic ruthenium(II) complex salt, [RuCl(Hobz)₂(PPh₃)]Cl (1) as well as the
paramagnetic ruthenium complex, [Ru̍ᴵ̍ᴵ̍ᴵCl(obs)₂(PPh₃)] (2). The X-ray crystal
structures of both metallic compounds confers a distorted octahedral geometry
imposed by the mutual ’2+2’ coordination modes of the chelators. DFT studies
indicated that the complex cation of 1 was more energetically favourable than the
neutral complex 2. Solid state ESR analysis of the paramagnetic complex 2 gave rise
to a distorted rhombic spectra whilst the liquid state ESR afforded an isotropic singlet
(at 298 K) and three distinctive signals (at 77 K).